Table 1 Definitions

Drug development process (DDP)

The consecutive series of early- to late-stage clinical trials that assess safety and efficacy of a new therapy

DDPs often consist of consecutive trials, from phase I trials to confirmatory studies

A new therapy is tested in a phase II trial that determines whether to advance the treatment to a phase III confirmatory trial

DDP segment

A subset of the DDP. In our illustration, the DDP segments consist of two consecutive clinical trials. The first of these trials is designed by the analyst and the results inform decisions about the second trial design

To simulate DDP segments, we specify scenarios and the statistical designs of two consecutive clinical trials. Simulations then provide a realistic representation of the DDP. The results from the first trial in the DDP segment inform relevant parameters, such as the sample size and enrollment criteria of the second study

A phase II trial with the primary aim of selecting the subpopulation that responds to the experimental treatment followed by a confirmatory trial that restricts enrollment only to the selected subpopulation

Performance metric

Operating characteristics of the DDP segment that illustrate the trade-off between costs, risks, time, and the likelihood of successfully developing the experimental therapy. Performance metrics across realistic scenarios can show whether study designs are aligned with the overall goals of the DDP and with the available resources. These metrics support the design of the first trial in the DDP segment based on its impact on the subsequent trial in the segment

Stylized simulations can be useful to estimate, under realistic scenarios, the numbers of patients to be enrolled in the DDP segment, the years to complete the segment, or the probability of a positive result of the DDP segment

The number of years necessary to complete a DDP segment